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Internal state drivers of behavioral flexibility and their underlying neural circuitry in the zona incerta

Project description

Exploring the zona incerta to understand internal state changes

Survival depends on the ability to quickly adapt behaviours to changing needs and environments. The zona incerta, a region of the brain, serves as a central hub, regulating essential functions such as defence and feeding while managing internal states. It helps compute behavioural changes and communicates them to drive action. The ERC-funded CERTASTATES project will use advanced technologies, including molecular techniques, in vivo mice imaging and behavioural assessments to investigate how specific cell types and circuits process changes in internal states, influence behavioural flexibility and can be modulated by deep brain stimulation. Focusing on the zona incerta, the project aims to enhance our understanding of how neural circuits generate and use internal states to guide adaptive behaviour.

Objective

Survival requires accurate and rapid implementation of adaptive behavior. In a world where our physiological needs and surrounding environment are ever changing, one wrong move could make the difference between life and death. How does the brain successfully compute changes in internal state and external cues, while factoring in experience, to drive the most appropriate behavioral outcome from moment-to-moment? Mounting evidence suggests that the zona incerta, a little studied region, is a central switchboard for such adaptive behavior. This subthalamic nucleus has widespread connections and was recently found to regulate an astounding range of behaviors critical for survival including defense, sleep, feeding and much more. It also encodes associated changes in internal states, such as anxiety, fatigue and hunger, and integrates sensory inputs across modalities. These features suggest that a central function of the zona incerta might be to locally compute needed transitions in behavior based on internal state changes, which are then broadcast to downstream targets to convert this into action. To address this hypothesis, CERTASTATES will employ cutting-edge molecular, circuit tracing, recording and in vivo imaging technologies in mice together with diverse behavioral paradigms and rich behavioral state readouts. The ultimate objective is to uncover how distinct internal state changes: (i) are processed in defined cell types and circuits, (ii) drive behavioral flexibility and (iii) are influenced by deep brain stimulation, motivated by the fact that the zona incerta is one of few established targets in humans for this therapeutic approach. Together, this work will advance our understanding of how neural circuits generate internal states, and in turn process, broadcast and use this information to guide adaptive behavior. Moreover, it will open an entry point for translation by exploring how clinically-applied neuromodulation can transform these vital computations.

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Programme(s)

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 494 634,00
Address
GESCHWISTER SCHOLL PLATZ 1
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 494 634,00

Beneficiaries (1)

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